Modeling of cardiac muscle thin films: Pre-stretch, passive and active behavior

Shim, Jongmin; Grosberg, Anna; Nawroth, Janna; Parker, Kevin Kit; Bertoldi, Katia

doi:10.1016/j.jbiomech.2011.11.024

Cited by 54 publications

(47 citation statements)

References 27 publications

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“…If the cells were allowed to settle with random orientation on the substrate, only a portion of the exerted force would contribute to deformation. In view of this issue, surface micro structuring was applied to enforce alignment of the cells in the desired direction [15]. In this way, the natural alignment in the native heart tissue is modeled as a highly desirable byproduct.…”

Section: Introductionmentioning

confidence: 99%

Mechano-Pharmacological Characterization of Cardiomyocytes Derived from Human Induced Pluripotent Stem Cells

Goßmann

Frotscher

Linder³

et al. 2016

Cell Physiol Biochem

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Background/Aims: Common systems for the quantification of cellular contraction rely on animal-based models, complex experimental setups or indirect approaches. The herein presented CellDrum technology for testing mechanical tension of cellular monolayers and thin tissue constructs has the potential to scale-up mechanical testing towards medium-throughput analyses. Using hiPS-Cardiac Myocytes (hiPS-CMs) it represents a new perspective of drug testing and brings us closer to personalized drug medication. Methods: In the present study, monolayers of self-beating hiPS-CMs were grown on ultra-thin circular silicone membranes and deflect under the weight of the culture medium. Rhythmic contractions of the hiPS-CMs induced variations of the membrane deflection. The recorded contraction-relaxation-cycles were analyzed with respect to their amplitudes, durations, time integrals and frequencies. Besides unstimulated force and tensile stress, we investigated the effects of agonists and antagonists acting on Ca²⁺ channels (S-Bay K8644/verapamil) and Na⁺ channels (veratridine/lidocaine). Results: The measured data and simulations for pharmacologically unstimulated contraction resembled findings in native human heart tissue, while the pharmacological dose-response curves were highly accurate and consistent with reference data. Conclusion: We conclude that the combination of the CellDrum with hiPS-CMs offers a fast, facile and precise system for pharmacological, toxicological studies and offers new preclinical basic research potential.

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Section: Introductionmentioning

confidence: 99%

Mechano-Pharmacological Characterization of Cardiomyocytes Derived from Human Induced Pluripotent Stem Cells

Goßmann

Frotscher

Linder³

et al. 2016

Cell Physiol Biochem

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“…The thin film undergoes deformation as a result of contraction when electrically stimulated. Optical recording of MTF contraction is filmed and the contractile forces of the tissue are calculated by analyzing the recording using a mathematical model (160, 161). This platform can be used for both smooth and striated muscle models.…”

Section: Applications Of Tissue Engineering In Modeling Of Cardiacmentioning

confidence: 99%

The Role of Tissue Engineering and Biomaterials in Cardiac Regenerative Medicine

Zhao

Feric

Thavandiran

et al. 2014

Canadian Journal of Cardiology

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In recent years, the development of three-dimensional engineered heart tissue (EHT) has made large strides forward due to advances in stem cell biology, materials science, pre-vascularization strategies and nanotechnology. As a result, the role of tissue engineering in cardiac regenerative medicine has become multi-faceted as new applications become feasible. Cardiac tissue engineering has long been established to have the potential to partially or fully restore cardiac function following cardiac injury. However, EHTs may also serve as surrogate human cardiac tissue for drug-related toxicity screening. Cardiotoxicity remains a major cause of drug withdrawal in the pharmaceutical industry. Unsafe drugs reach the market because pre-clinical evaluation is insufficient to weed out cardiotoxic drugs in all their forms. Bioengineering methods could provide functional and mature human myocardial tissues, i.e. physiologically relevant platforms, for screening the cardiotoxic effects of pharmaceutical agents and facilitate the discovery of new therapeutic agents. Finally, advances in induced pluripotent stem cells have made patient-specific EHTs possible, which opens up the possibility of personalized medicine. Herein, we give an overview of the present state of the art in cardiac tissue engineering, the challenges to the field and future perspectives.

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“…The active muscle fibers are represented by discrete truss elements requiring each fiber be defined, which can be a time consuming process, especially for non-rectangular geometries. Shim et al (2012) model a similar biohybrid film, utilizing a continuum material model of rat cardiomyocytes in an explicit finite element code. The explicit solver simplifies the model implementation, but at the cost of accuracy and, possibly, computational efficiency.…”

Section: Introductionmentioning

confidence: 99%

Modeling Bioactive Materials

Dorfmann

Paetsch

2015

Nonlinear Mechanics of Soft Fibrous Materials

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Abstract. In this chapter we examine the mechanical properties of the ventral interior lateral muscle of the tobacco hornworm caterpillar, Manduca sexta. Uniaxial loading-unloading shows that the tissue is capable of large nonlinear pseudo-elastic deformations, has a hysteretic behavior and displays stress softening during the first few cycles of repeated loading. The data are used to develop a constitutive model that accounts for the observed material response, including a continuous transition from passive to active states. We consider the material initially incompressible, pseudo-elastic and transversely isotropic with preferred orientation parallel to the longitudinal direction of the muscle. The constitutive formulation is then generalized to account for slightly compressible materials and adapted for finite element implementation. The corresponding incremental equations and the associated isochoric and volumetric parts of the elasticity tensor are derived. To account for pseudoelasticty, the isochoric part is modified accordingly. The simulation of a bio-actuated micro-pump is used to validate and demonstrate the capability of the model.

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Modeling of cardiac muscle thin films: Pre-stretch, passive and active behavior

Cited by 54 publications

References 27 publications

Mechano-Pharmacological Characterization of Cardiomyocytes Derived from Human Induced Pluripotent Stem Cells

Mechano-Pharmacological Characterization of Cardiomyocytes Derived from Human Induced Pluripotent Stem Cells

The Role of Tissue Engineering and Biomaterials in Cardiac Regenerative Medicine

Modeling Bioactive Materials

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